Meiosis is a special type of cell division that yields haploid gametes via a complex pathway that likely requires hundreds of genes, some of which are specified to meiotic cells and others which are ubiquitous in their expression. In diverse organisms from yeast to mice, mutations in many genes may lead to meiosis-specific defects or lead to defects in meiosis that are associated with somatic cell defects such as tumors caused by defective DNA repair. Although it is likely that meiosis is conserved throughout evolution, little is known about the genetics of meiosis in humans even though it is likely that meiotic arrest associated with azoospermia (the production of no sperm) or oligospermia (the production of less that one million sperm/ml) may be common. This observation has prompted Dr. Reijo to address the questions: 1) Are some men with very low or no sperm counts mosaic for deletions of the Deleted in AZoospermia genes which are implicated in progression through meiosis? 2) Do some men with very low numbers of sperm have a defect in recombination or DNA repair? If so, are these defects being bypassed in efforts to propagate children in the clinic without regard to other deleterious effects that may present later in life? In this work, their overall hypothesis is that defects in genes involved in meiosis, such as DAZ, and those required for recombination and DNA repair may cause meiotic arrest (at a pachytene I checkpoint) in men just as defects in these genes cause meiotic arrest in other organisms. Their research over the last four years established that many cases of infertility in men are genetic and that infertility can be passed from father to son via current clinical practice. More recently they have collected preliminary data that suggest that DNA repair defects occur more frequently in infertile men with meiotic arrest than in fertile men. They propose to extend their findings and use their new technology in the genetics of human reproduction by using single sperm PCR to examine the germ cells of infertile men for DAZ deletions and defects in DNA repair and recombination.